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BioMed Research International
Volume 2014 (2014), Article ID 495789, 13 pages
Review Article

The Purinergic System and Glial Cells: Emerging Costars in Nociception

1Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti, 9-20133 Milan, Italy
2Department of Drug Discovery and Development (D3), Italian Institute of Technology (IIT), Via Morego, 30-16163 Genoa, Italy

Received 28 May 2014; Accepted 8 July 2014; Published 3 September 2014

Academic Editor: Livio Luongo

Copyright © 2014 Giulia Magni and Stefania Ceruti. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


It is now well established that glial cells not only provide mechanical and trophic support to neurons but can directly contribute to neurotransmission, for example, by release and uptake of neurotransmitters and by secreting pro- and anti-inflammatory mediators. This has greatly changed our attitude towards acute and chronic disorders, paving the way for new therapeutic approaches targeting activated glial cells to indirectly modulate and/or restore neuronal functions. A deeper understanding of the molecular mechanisms and signaling pathways involved in neuron-to-glia and glia-to-glia communication that can be pharmacologically targeted is therefore a mandatory step toward the success of this new healing strategy. This holds true also in the field of pain transmission, where the key involvement of astrocytes and microglia in the central nervous system and satellite glial cells in peripheral ganglia has been clearly demonstrated, and literally hundreds of signaling molecules have been identified. Here, we shall focus on one emerging signaling system involved in the cross talk between neurons and glial cells, the purinergic system, consisting of extracellular nucleotides and nucleosides and their membrane receptors. Specifically, we shall summarize existing evidence of novel “druggable” glial purinergic targets, which could help in the development of innovative analgesic approaches to chronic pain states.